Recently, for the purpose of preventing a nosocomial infection caused by contacting an infusion solution with intrahospital air, a closed system has been applied, where a glass bottle is substituted by a flexible plastic container, such as a polyvinyl chloride bag, so as not to develop a negative pressure with the discharge of an infusion solution. The plastic container is required to have a flexibility capable of following the discharge of the infusion solution, transparency allowing the observation of foreign materials and residual volume of infusion solution, thermal resistance capable of resisting sterilization, resistance to impacts so as not to be broken in physical distribution and handling, high oxygen gas barrier so that the infusion solution does not deteriorate, and adaptability to various laws, particularly Japanese Pharmacopoeia, 14th Revision, etc.
Conventional plastic containers for infusion solution are single layer containers in bag-shapes or blow-molding bottle-shapes and made of polyvinyl chloride, polyethylene, polypropylene or the like. The single layer containers are inferior as an oxygen gas barrier, although they satisfy other requirements.
It is possible to consider the lamination of an oxygen gas barrier layer for imparting oxygen gas barrier ability to the containers. In general, an oxygen gas barrier layer is laminated by dry lamination using a polyurethane adhesive. As a result, residual solvent and unreacted materials of the polyurethane adhesive elute into the infusion solution in the bag and it cannot pass the elution test in Japanese Pharmacopoeia, 14th Revision. A conventional curing agent for a polyurethane adhesive is toluene diisocyanate because of its fast reaction rate. However, toluene diisocyanate is prohibited by the FDA in the US because it converts to toluene diamine, which has carcinogenicity, during sterilization. Then, the curing agent is changed to an aliphatic isocyanate of which the reaction rate is slow, causing an increase in unreacted materials. Thus, plastic containers having an oxygen gas barrier layer have not been used as infusion solution bags.
As mentioned above, since single layer plastic containers are inferior in oxygen gas barrier ability, various techniques for preventing oxidation of the infusion solution have been developed.
JP2-46450B discloses the sterilization of an infusion solution, such as amino acids, fats, sugars or electrolytes, in an oxygen-free high pressure water vapor pressurized by an inert gas, in order to prevent deterioration by oxidation. After cooling, the infusion solution bag is vacuum-packaged or N2 gas-packaged by a second package having a high oxygen gas barrier ability.
Amino acid infusion solutions and fat infusion solutions are liable to deteriorate by oxidation. Particularly, in the case of amino acid infusion solutions, a bisulfite or sulfite, such as NaHSO3′ or Na2SO3, is frequently added as an antioxidant in order to prevent coloring and production of insoluble indole compounds by the oxidation of tryphtophan, which is an essential amino acid. However, it is known that when an infusion solution containing sulfite ions is administered to a patient with hypersensitive diathesis or an atopic patient, the sulfite ions induce an allergic reaction, such as urticaria, bronchosposm or anaphylactic shock, from the patient. Accordingly, the presence of a sulfite is undesirable.
However, this technique has problems in the cost for the use of N2 gas, restriction in working due to, unless packaging by a second package occurs immediately after sterilization, followed by cooling, deterioration proceeds, although the packaging by the second package is, in general, carried out as a transverse pillow-type, tunneling occurs at the meeting portion of a back seal with a transverse seal in this type to generate pinholes. When breakage or pinholes are generated in the second package during distribution or handling, the infusion solution is deteriorated by oxidation caused by entering air and extra cost is required for double packaging, and the use of sulfite ions, which is still required, nevertheless, is undesirable for the human body.
JP4-282162A discloses that a sterilized infusion solution in a plastic container is further packaged by a package having a high oxygen gas barrier ability, and an oxygen scavenger (“Age Less”, Mitsubishi Chemicals) is placed therebetween.
JP4-295368A discloses that an infusion solution bag is first packaged with a package having a high oxygen gas barrier ability and an oxygen scavenger is placed therebetween. Then, the double package is sterilized and used for distribution as is. JP8-34729B discloses that, after sterilization, the oxygen gas barrier package and oxygen scavenger are changed by a second package having a high oxygen gas barrier ability and a new oxygen scavenger to prevent deterioration by oxidation.
However, the above techniques disclosed in JP4-282162A, JP4-295368A, JP8-34729B also have problems in transverse pillow-type packages, i.e. tunneling occurring at the meeting portion of a back seal with a transverse seal to generate pinholes. When breakage or pinholes are generated in the second package during distribution or handling, the infusion solution is deteriorated by oxidation caused by entering air and extra cost and labor are required for inserting an oxygen scavenger, and the use of sulfite ions, which is still required, nevertheless, is undesirable for the human body.
When plural infusion solutions, such as amino acids, fats, sugars or electrolytes, are administered simultaneously, they are suitably mixed on administration according to the condition of the disease. However, such a mixing in a hospital is troublesome and it is possible to cause contamination with bacteria and, accordingly, is unsanitary. Some techniques have been developed for mixing plural infusion solutions sanitarily by providing plural chambers divided by communicable barriers, each chamber containing a different infusion solution, and being allowed to communicate with each other on administration (Japanese Patent Nos. 2699212 and 3049280, JP2003-212767A).
However, the above techniques of providing plural chambers divided by communicable barriers have also the problems mentioned above.